Spatial and temporal analysis of the risks posed by total petroleum hydrocarbon and trace element contaminants in coastal waters of Kuwait.

Nine trace elements including As, Cd, Cu, Fe, Hg, Ni, Pb, V and Zn, and total petroleum hydrocarbons were analysed from water samples collected from 23 stations since 1984 from Kuwaiti coastal waters. Here it was investigated whether concentrations of these determinants are at levels above Kuwaiti and internationally established assessment criteria (AC). The results indicate that Cu and Cd had the most Kuwaiti AC breaches over time. Comparing the data of the last sampled year to the least stringent international AC, then Cu and Cd showed breaches at all stations. The trends for trace metals are significantly downwards, especially for Cd and Hg. No determinant measured showed a significant upward trend, indicating that water pollution for these contaminants is not a worsening situation. However, further sampling should be carried out to confirm these findings, especially at shoreline locations, where routine monitoring ceased in 2011 to investigate any recent changes.

Immunohistochemical detection of multidrug resistance protein in human lung cancer and normal lung.

Monoclonal antibody QCRL-1 is highly specific for a defined linear epitope in a relatively poorly conserved region of the human multidrug resistance protein (MRP). We have used QCRL-1 to examine MRP expression in archival and fresh snap-frozen samples of untreated small cell (SC) and non-small cell (NSC) lung cancers (LCs), as well as normal lung. We found that the majority (87%) of all histological subtypes of NSCLC had detectable levels of MRP in most of the tumor mass. In a substantial proportion of adenocarcinomas (55%) and squamous cell carcinomas (28%), immunoreactivity approached that obtained with the highly multidrug resistant cell line H69AR from which the MRP was originally cloned. Both the level and frequency of MRP expression in untreated SCLC was significantly lower than in NSCLC. The MRP was detectable in only 56% of SCLC tumors and, in most cases, was expressed in small focal clusters of cells. Immunofluorescence studies of tumor tissue and normal lung confirmed the plasma membrane location of the MRP. However, in normal bronchial epithelium and seromucous glands, unlike in tumor cells, the MRP was detected only on basolateral membranes. In addition, strong MRP immunoreactivity was detected in reactive type II pneumocytes present in hyperplastic alveoli, but not in normal type I and type II pneumocytes. No potentially confounding correlation independent of its possible role in drug resistance was observed between MRP expression in untreated NSCLC and any clinicopathological parameter examined, including overall survival.

Synthesis, DNA binding, cytotoxicity and sequence specificity of a series of imidazole-containing analogs of the benzoic acid mustard distamycin derivative tallimustine containing an alkylating group at the C-terminus.

In an attempt to produce additional alkylation and crosslinking in the minor groove of DNA, imidazole-containing analogs of distamycin were synthesized with benzoic acid mustard (BAM) and methoxyaziridinyl moieties present at the N- and C-termini, respectively. Analogs 1a-c differed in the number of methylene units (2-4 respectively) between the C-terminal carbonyl group and the methoxyaziridinyl moiety. DNA binding affinity to several polynucleotides decreased with increasing linker length, whereas DNA interstrand crosslinking ability, as measured by a plasmid gel based assay, increased. The in vitro cytotoxicity in human chronic myeloid leukemia K562 cells and the panel of human tumor cell lines at the National Cancer Institute decreased with increasing number of methylene units, and no increase in cytotoxicity was observed over compound AR-1-122 which did not contain the methoxyaziridinyl moiety. 1a-c had the same sequence selectivity of alkylation as AR-1-122, showing alkylation only at 5'-TTTTGPu sequences. The relative binding to these sequences decreased with increasing number of methylene units. The addition of a methoxyaziridinyl moiety in this group of imidazole and BAM-containing compounds can, therefore, increase crosslinking ability to naked DNA but this does not result in an increase in cytotoxicity. In contrast the cytotoxicity was related to their ability to produce sequence specific alkylation at 5'-TTTTGPu sequences.

Structure-activity relationship of a series of C-terminus modified aminoalkyl, diaminoalkyl- and anilino-containing analogues of the benzoic acid mustard distamycin derivative tallimustine: synthesis, DNA binding and cytotoxicity studies.

As part of our investigations into the design of more cytotoxic analogues of the experimental anticancer drug tallimustine, 1, C-terminus modified aminoalkyl-, 2a-c, diaminoalkyl-, 3, and anilino-containing, 4, derivatives have been synthesized. Compounds 2a-c differ by 2, 3, or 4 methylene units in the C-terminus, respectively. Results from an ethidium displacement study on poly(dA-dT), poly(dG-dC), calf thymus DNA and T4 coliphage DNA showed that compounds 2-4 interact in the minor groove of the polynucleotides with a preference for poly(dA-dT) over poly(dG-dC). Compound 4 bound more weakly to the DNAs than 2a-c and 3. Using a CD dilution assay compounds 2a-c and 3 were demonstrated to bind irreversibly to calf thymus DNA. The sequence selectivity by which compounds 2-4 alkylate DNA was demonstrated using a Taq polymerase stop assay. All the compounds alkylated preferentially at the 3'-purine residue in a 5'-TTTTGPu-3' sequence (Pu = A or G). This observed sequence specificity is similar to that of tallimustine and a related compound 5. At an equimolar concentration the aminoalkyl compounds 2a-c (2b > 2a > 2c), and diaminoalkyl compound 3 were more efficient at alkylating these sequences than the anilino compound 4. Following a one hour exposure of human chronic myeloid leukemia K562 cells, compounds 2b and 3 have lower IC50 values (1.64 microM and 3.03 microM, respectively) than tallimustine (5 microM) and similar values to a related compound 5 (2.2 microM). The order of cytotoxicity for all the compounds is 2b > 5 > 3 > 2a > 1 > 2c = 4. These results indicate that the cytotoxicities of these compounds are related to their relative ability to alkylate the consensus DNA binding sequence.

Individuals with schizophrenia have an increased incidence of the H2R649G allele for the histamine H2 receptor gene.

We have previously described an allelic variant of the human H2R, nominated the H2R649G allele. This allele contains an adenine-->guanidine substitution at base 649, which introduces an additional TaqI restriction endonuclease site into the gene. With this in mind, we have investigated allelic polymorphism of this receptor and its association with schizophrenia. H2R DNA from 47 schizophrenic patients and 46 control subjects was amplified by the polymerase chain reaction (PCR). These PCR products were analyzed by observing TaqI cleavage patterns and single-stranded conformational polymorphisms. It was found that the H2R649G allele was 1.8 times more frequent in the schizophrenic population (chi 2 test P < 0.01). In addition, schizophrenic individuals were 2.8 times more likely to be homozygous for the H2R649G allele than the control population, (chi 2 test P < 0.05). These data place the attributable fraction for possession of the H2R649G allele at 28.4%.

Allelic variations of the human histamine H2 receptor gene.

The gene encoding the human histamine H2 receptor (H2R) has previously been cloned and sequenced from gastric cDNA. Following PCR amplification of a fragment of the H2R gene from total human DNA, three single nucleotide base substitutions were observed and confirmed when compared with the previously published sequence. One of these base changes introduces an additional TaqI restriction endonuclease site in the coding portion of the gene. PCR amplification of human H2R gene fragments followed by cleavage with TaqI demonstrated the existence of allelic variation of the human H2R gene.

Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus.

The neural basis underlying the cognitive side effects of ECT is unknown. Recent studies suggest that the memory dysfunction may be caused by alterations in hippocampal synaptic efficacy [20]. In situ hybridisation was used to examine the possible receptor mechanisms responsible for this effect. Repeated ECS markedly increased mRNA expression for the GluR1 subunit of the AMPA receptor, but not the NMDAR1A-G subtypes of the NMDA receptor, relative to control treatments. This effect was present 24 h after the last seizure and may be responsible for the expression of the ECS-induced increase in synaptic efficacy.

Corrosion behavior of Au and Ag modified Cu-Ni-Mn alloys.

The linear electrochemical polarization method was used to provide quantitative in vitro measurements of corrosion rates as a function of exposure time for Cu-Ni-Mn, Cu-Ni-Mn-Au, Cu-Ni-Mn-Ag, and Cu-Ni-Mn-Au-Ag alloys in artificial saliva. Both Au and Ag additives to dental-cast Cu-Ni-Mn alloys lowered the corrosion rate significantly.